scholarly journals Male infertility due to testicular disorders

2020 ◽  
Author(s):  
Aditi Sharma ◽  
Suks Minhas ◽  
Waljit S Dhillo ◽  
Channa N Jayasena
Keyword(s):  
Male Infertility ◽  
Evidence Synthesis ◽  
Causative Factor ◽  
Severe Form ◽  
Molecular Diagnostic ◽  
Future Research ◽  
Testicular Sperm Extraction ◽  
Hormonal Stimulation ◽  
Estrogen Receptor Modulators ◽  
Testicular Failure

Abstract Context Male infertility is defined as the inability to conceive following 1 year of regular unprotected intercourse. It is the causative factor in 50% of couples and a leading indication for assisted reproductive techniques (ART). Testicular failure is the most common cause of male infertility, yet the least studied to date. Evidence Acquisition The review is an evidence-based summary of male infertility due to testicular failure with a focus on etiology, clinical assessment, and current management approaches. PubMed-searched articles and relevant clinical guidelines were reviewed in detail. Evidence Synthesis/Results Spermatogenesis is under multiple levels of regulation and novel molecular diagnostic tests of sperm function (reactive oxidative species and DNA fragmentation) have since been developed, and albeit currently remain as research tools. Several genetic, environmental, and lifestyle factors provoking testicular failure have been elucidated during the last decade; nevertheless, 40% of cases are idiopathic, with novel monogenic genes linked in the etiopathogenesis. Microsurgical testicular sperm extraction (micro-TESE) and hormonal stimulation with gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors are recently developed therapeutic approaches for men with the most severe form of testicular failure, nonobstructive azoospermia. However, high-quality clinical trials data is currently lacking. Conclusions Male infertility due to testicular failure has traditionally been viewed as unmodifiable. In the absence of effective pharmacological therapies, delivery of lifestyle advice is a potentially important treatment option. Future research efforts are needed to determine unidentified factors causative in “idiopathic” male infertility and long-term follow-up studies of babies conceived through ART.

The Role of Hormone Stimulation in Men With Nonobstructive Azoospermia Undergoing Surgical Sperm Retrieval

2020 ◽  
Vol 105 (12) ◽  
pp. e4896-e4906
Author(s):  
Tharu Tharakan ◽  
Andrea Salonia ◽  
Giovanni Corona ◽  
Waljit Dhillo ◽  
Suks Minhas ◽  
...  
Keyword(s):  
Severe Form ◽  
Current Evidence ◽  
Testicular Sperm Extraction ◽  
Nonobstructive Azoospermia ◽  
Sperm Retrieval ◽  
Hormonal Stimulation ◽  
Estrogen Receptor Modulators ◽  
Biological Children ◽  
First Time

Abstract Nonobstructive azoospermia, (NOA) is the most common cause of azoospermia. NOA is characterized by hypergonadotropic hypogonadism, testicular failure, and impaired spermatogenesis. The recent development of surgical sperm retrieval techniques such as microsurgical testicular sperm extraction (mTESE) has, for the first time, allowed some men with NOA to father biological children. It is common practice for endocrine stimulation therapies such as gonadotropins, selective estrogen receptor modulators (SERMs), and aromatase inhibitors to be used prior to mTESE to increase intratesticular testosterone synthesis with the aim of improving sperm retrieval rates; however, there is currently a paucity of data underpinning their safety and efficacy. We present 2 cases of men with NOA undergoing endocrine stimulation therapy and mTESE. We also discuss the current evidence and controversies associated with the use of hormonal stimulation therapy in couples affected by this severe form of male infertility.

scholarly journals Novel Variants in HFM1 Lead to Male Infertility Due to Non-obstructive Azoospermia

2021 ◽  
Author(s):  
Dongdong Tang ◽  
Mingrong Lv ◽  
Yang Gao ◽  
Huiru Cheng ◽  
Kuokuo Li ◽  
...  
Keyword(s):  
Male Infertility ◽  
Y Chromosome ◽  
Testicular Biopsy ◽  
Severe Form ◽  
Testicular Sperm Extraction ◽  
Obstructive Azoospermia ◽  
Sperm Retrieval ◽  
Gene Variation ◽  
Y Chromosome Microdeletions ◽  
Whole Exome

Abstract Background Non-obstructive azoospermia (NOA) is the most severe form of male infertility. More than half of the NOA patients were idiopathic for their etiology, in whom it’s difficult to retrieve sperm despite the application of microsurgical testicular sperm extraction (microTESE). Therefore, we conducted to this study to identify the potential genetic factors responsible for NOA, and investigate the sperm retrieval rate of microTESE for the genetic defected NOA.Methods One NOA patient from a consanguineous family (F1-II-1) and fifty NOA patients from non-consanguineous families were included in the study. Semen analyses, chromosome karyotypes, screening of Y chromosome microdeletions, sex hormone testing, and subsequent testicular biopsy were performed to categorize NOA or obstructive azoospermia. Potentialgenetic variants were identified by whole exome sequencing (WES),and confirmed by Sanger sequencing in F1 II-1. The candidate genes were screened in the other fifty NOA patients. Further experiments including quantitative real time-polymerase chain reaction and western blotting were performed to verify the effects of gene variation on gene expression.Results Normal somatic karyotypes and Y chromosome microdeletions were examined in all patients. Hematoxylin and eosin staining (H&E) of the testicular tissues suggested meiotic arrest, and a novel homozygous HFM1 variant (c.3490C>T: p.Q1164X) was identified in F1 II-1. Furthermore, another homozygous HFM1 variant (c.3470G>A: p.C1157Y) was also verified in F2 II-1 from the fifty NOA patients. Significantly decreased expression levels of HFM1 mRNA and protein were observed in the testicular tissues of these two mutants compared with controls. MicroTESE was performed in these two patients, while no sperm were retrieved. Conclusions Our study identified two novel homozygous variants of HFM1 that are responsible for spermatogenic failure and NOA, even microTESE can not contribute to retrieve sperm in these patients.

scholarly journals Novel variants in helicase for meiosis 1 lead to male infertility due to non-obstructive azoospermia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dongdong Tang ◽  
Mingrong Lv ◽  
Yang Gao ◽  
Huiru Cheng ◽  
Kuokuo Li ◽  
...  
Keyword(s):  
Male Infertility ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Factors ◽  
Testicular Biopsy ◽  
Severe Form ◽  
Testicular Sperm Extraction ◽  
Obstructive Azoospermia ◽  
Sperm Retrieval ◽  
Whole Exome

Abstract Background Non-obstructive azoospermia (NOA) is the most severe form of male infertility; more than half of the NOA patients are idiopathic. Although many NOA risk genes have been detected, the genetic factors for NOA in majority of the patients are unknown. In addition, it is difficult to retrieve sperm from these patients despite using the microsurgical testicular sperm extraction (microTESE) method. Therefore, we conducted this genetic study to identify the potential genetic factors responsible for NOA and investigate the sperm retrieval rate of microTESE for genetically deficient NOA patients. Methods Semen analyses, sex hormone testing, and testicular biopsy were performed to categorize the patients with NOA. The chromosome karyotypes and Y chromosome microdeletion analyses were used to exclude general genetic factors. Whole exome sequencing and Sanger sequencing were performed to identify potential genetic variants in 51 patients with NOA. Hematoxylin and eosin staining (H&E) and anti-phosphorylated H2AX were used to assess the histopathology of spermatogenesis. Quantitative real time-polymerase chain reaction, western blotting, and immunofluorescence were performed to verify the effects of gene variation on expression. Results We performed whole exome sequencing in 51 NOA patients and identified homozygous helicase for meiosis 1(HFM1) variants (NM_001017975: c.3490C > T: p.Q1164X; c.3470G > A: p.C1157Y) in two patients (3.9%, 2/51). Histopathology of the testis showed that spermatogenesis was completely blocked at metaphase in these two patients carrying the HFM1 homozygous variants. In comparison with unaffected controls, we found a significant reduction in the levels of HFM1 mRNA and protein expression in the testicular tissues from these two patients. The patients were also subjected to microTESE treatment, but the sperms could not be retrieved. Conclusions This study identified novel homozygous variants of HFM1 that are responsible for spermatogenic failure and NOA, and microTESE did not aid in retrieving sperms from these patients.

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

scholarly journals High expression of neutrophil and monocyte CD64 with simultaneous lack of upregulation of adhesion receptors CD11b, CD162, CD15, CD65 on neutrophils in severe COVID-19

2021 ◽  
Vol 8 ◽  
pp. 204993612110340
Author(s):  
Malgorzata Karawajczyk ◽  
Lena Douhan Håkansson ◽  
Miklos Lipcsey ◽  
Michael Hultström ◽  
Karlis Pauksens ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Mean Fluorescence Intensity ◽  
Immune Dysfunction ◽  
Severe Form ◽  
Receptor Expression ◽  
Future Research ◽  
Early Biomarkers ◽  
Severe Stage ◽  
Activated Neutrophils ◽  
Edta Blood

Background and Aims: The pronounced neutrophilia observed in patients with coronavirus disease 2019 (COVID-19) infections suggests a role for these leukocytes in the pathology of the disease. Monocyte and neutrophil expression of CD64 and CD11b have been reported as early biomarkers to detect infections. The aim of this study was to study the expression of receptors for IgG (CD64) and adhesion molecules (CD11b, CD15s, CD65, CD162, CD66b) on neutrophils and monocytes in patients with severe COVID-19 after admission to an intensive care unit (ICU). Methods: The expression of receptors was analyzed using flow cytometry. EDTA blood from 23 patients with confirmed COVID-19 infection was sampled within 48 h of admission to the ICU. Leukocytes were labeled with antibodies to CD11b, CD15s, CD65s, CD162, CD64, and CD66b. Expression of receptors was reported as mean fluorescence intensity (MFI) or the percentage of cells expressing receptors. Results: Results are presented as comparison of COVID-19 patients with the healthy group and the receptor expression as MFI. Neutrophil receptors CD64 (2.5 versus 0.5) and CD66b (44.5 versus 34) were increased and CD15 decreased (21.6 versus 28.3) when CD65 (6.6 versus 4.4), CD162 (21.3 versus 21.1) and CD11b (10.5 versus 12) were in the same range. Monocytes receptors CD64 (30.5 versus 16.6), CD11b (18.7 versus 9.8), and CD162 (38.6 versus 36.5) were increased and CD15 decreased (10.3 versus 17.9); CD65 were in the same range (2.3 versus 1.96). Conclusion: Monocytes and neutrophils are activated during severe COVID-19 infection as shown by strong upregulation of CD64. High monocyte and neutrophil CD64 can be an indicator of a severe form of COVID19. The adhesion molecules (CD11b, CD162, CD65, and CD15) are not upregulated on otherwise activated neutrophils, which might lead to relative impairment of tissue migration. Low adhesion profile of neutrophils suggests immune dysfunction of neutrophils. Monocytes maintain upregulation of some adhesion molecules (CD11b, CD162) suggesting the persistence of an increased ability to migrate into tissues, even during a severe stage of COVID-19. Future research should focus on CD64 and CD11b kinetics in the context of prognosis.

scholarly journals Hormonal Treatment of Men with Nonobstructive Azoospermia: What Does the Evidence Suggest?

2021 ◽  
Vol 10 (3) ◽  
pp. 387 ◽  
Author(s):  
Ettore Caroppo ◽  
Giovanni M. Colpi
Keyword(s):  
Current Knowledge ◽  
Hormonal Treatment ◽  
Hormonal Control ◽  
Testicular Sperm Extraction ◽  
Nonobstructive Azoospermia ◽  
Sperm Retrieval ◽  
Hormonal Stimulation ◽  
Testosterone Levels ◽  
Retrieval Rate ◽  
Standard Clinical Practice

Hormonal stimulation of spermatogenesis prior to surgery has been tested by some authors to maximize the sperm retrieval yield in patients with nonobstructive azoospermia. Although the rationale of such an approach is theoretically sound, studies have provided conflicting results, and there are unmet questions that need to be addressed. In the present narrative review, we reviewed the current knowledge about the hormonal control of spermatogenesis, the relationship between presurgical serum hormones levels and sperm retrieval rates, and the results of studies investigating the effect of hormonal treatments prior to microdissection testicular sperm extraction. We pooled the available data about sperm retrieval rate in patients with low vs. normal testosterone levels, and found that patients with normal testosterone levels had a significantly higher chance of successful sperm retrieval compared to those with subnormal T levels (OR 1.63, 95% CI 1.08–2.45, p = 0.02). These data suggest that hormonal treatment may be justified in patients with hypogonadism; on the other hand, the available evidence is insufficient to recommend hormonal therapy as standard clinical practice to improve the sperm retrieval rate in patients with nonobstructive azoospermia.

scholarly journals Spinal cord injury and male infertility—a review of current literature, knowledge gaps, and future research

2018 ◽  
Vol 7 (S3) ◽  
pp. S373-S382 ◽  
Author(s):  
Ross Anderson ◽  
Rachel Moses ◽  
Sara Lenherr ◽  
James M. Hotaling ◽  
Jeremy Myers
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Male Infertility ◽  
Current Literature ◽  
Future Research ◽  
Knowledge Gaps ◽  
Cord Injury

scholarly journals Effects of Environmental and Pathological Hypoxia on Male Fertility

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhibin Li ◽  
Sumin Wang ◽  
Chunli Gong ◽  
Yiyang Hu ◽  
Jiao Liu ◽  
...  
Keyword(s):  
Male Infertility ◽  
Animal Studies ◽  
Sperm Quality ◽  
Reproductive Toxicity ◽  
Causative Factor ◽  
Reproductive Hormones ◽  
Epigenetic Changes ◽  
Causal Association ◽  
Spermatogenic Cells ◽  
Male Population

Male infertility is a widespread health problem affecting approximately 6%–8% of the male population, and hypoxia may be a causative factor. In mammals, two types of hypoxia are known, including environmental and pathological hypoxia. Studies looking at the effects of hypoxia on male infertility have linked both types of hypoxia to poor sperm quality and pregnancy outcomes. Hypoxia damages testicular seminiferous tubule directly, leading to the disorder of seminiferous epithelium and shedding of spermatogenic cells. Hypoxia can also disrupt the balance between oxidative phosphorylation and glycolysis of spermatogenic cells, resulting in impaired self-renewal and differentiation of spermatogonia, and failure of meiosis. In addition, hypoxia disrupts the secretion of reproductive hormones, causing spermatogenic arrest and erectile dysfunction. The possible mechanisms involved in hypoxia on male reproductive toxicity mainly include excessive ROS mediated oxidative stress, HIF-1α mediated germ cell apoptosis and proliferation inhibition, systematic inflammation and epigenetic changes. In this review, we discuss the correlations between hypoxia and male infertility based on epidemiological, clinical and animal studies and enumerate the hypoxic factors causing male infertility in detail. Demonstration of the causal association between hypoxia and male infertility will provide more options for the treatment of male infertility

Scapular Kinematics and Subacromial-Impingement Syndrome: A Meta-Analysis

2012 ◽  
Vol 21 (4) ◽  
pp. 354-370 ◽  
Author(s):  
Mark K. Timmons ◽  
Chuck A. Thigpen ◽  
Amee L. Seitz ◽  
Andrew R. Karduna ◽  
Brent L. Arnold ◽  
...  
Keyword(s):  
General Population ◽  
Evidence Synthesis ◽  
Impingement Syndrome ◽  
Subacromial Impingement Syndrome ◽  
Lead Author ◽  
Future Research ◽  
Scapular Kinematics ◽  
Arm Elevation ◽  
The Impact ◽  
Scapular Plane

Context:The literature does not present a consistent pattern of altered scapular kinematics in patients with shoulder-impingement syndrome (SIS).Objectives:To perform meta-analyses of published comparative studies to determine the consistent differences in scapular kinematics between subjects with SIS and controls. In addition, the purpose was to analyze factors of the data-collection methods to explain the inconsistencies in reported kinematics. The results of this study will help guide future research and enable our understanding of the relationship between scapular kinematics and SIS.Evidence Acquisition:A search identified 65 studies; 9 papers met inclusion criteria. Sample sizes, means, and SDs of 5 scapular-kinematic variables were extracted or obtained from each paper’s lead author. Standard difference in the mean between SIS and controls was calculated. Moderator variables were plane of arm elevation, level of arm elevation (ARM) and population (POP).Evidence Synthesis:Overall, the SIS group had less scapular upward rotation (UR) and external rotation (ER) and greater clavicular elevation (ELE) and retraction (RET) but no differences in scapular posterior tilt (PT). In the frontal plane, SIS subjects showed greater PT and ER, and in the scapular plane, less UR and ER and greater ELE and RET. There was also greater ELE and RET in the sagittal plane. There was less UR at the low ARM and greater ELE and RET at the high ARM with SIS. Athletes and overhead workers showed less UR, while athletes showed greater PT and workers showed less PT and ER. The general population with SIS had greater ELE and RET only.Conclusions:Subjects with SIS demonstrated altered scapular kinematics, and these differences are influenced by the plane, ARM, and POP. Athletes and overhead workers have a different pattern of scapular kinematics than the general population. The scapular plane is most likely to demonstrate altered kinematics. These factors should be considered when designing futures studies to assess the impact of altered kinematics in patients with SIS.

Reviews of evidence

2018 ◽  
pp. 221-232
Author(s):  
Alan J. Silman ◽  
Gary J. Macfarlane ◽  
Tatiana Macfarlane
Keyword(s):  
Information Overload ◽  
Evidence Synthesis ◽  
Scientific Evidence ◽  
Epidemiological Studies ◽  
Future Research ◽  
Scientific Journals ◽  
Search Terms ◽  
The Us ◽  
Scientific Topic

The preceding chapters have focused on the generation of scientific evidence using epidemiological studies. Here the emphasis is on bringing together evidence (evidence synthesis) to inform future research and health policies. The chapter considers levels and quality of scientific evidence and describes in detail how to conduct a systematic review. It reviews the ways of summarizing and evaluating evidence from epidemiological studies. Summary of evidence is needed in everyday clinical practice and for public health. We live in a time of information overload, and it is impossible to read all the available scientific journals, even on a narrow scientific topic. Simply using search terms such as ‘cancer’ will result in millions of results in Google Scholar or PubMed (a service of the US National Library of Medicine®) database. Given the ever-increasing volume of medical literature and time constraints, summary of evidence plays a big role in decision-making.

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